The purpose of the project is to collect information about the sensitivity of hyperplastic nodules in the liver of ethionine-fed rats to acute and chronic effects of ethionine. The development of areas of hyperplasia and of hyperplastic nodules is regarded as the most important precancerous step in hepatocarcinogenesis, and apparently the hyperplastic nodules are resistant to some toxic effects of DL-ethionine. It was found that the concentration of L-ethionine and its metabolites was significantly increased in hyperplastic nodules and adjacent liver tissue compared to normal liver tissue. This increase is accompanied by a decrease in the synthesis of S-adenosylethionine and by a decrease in the capacity to acetylate both ethionine sulfoxide and ethionine to N-acetyl derivatives. The mechanism of the decrease of the activity of S-adenosylmethionine synthetase is being investigated.